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The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death
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Journal Article
The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death
2025
Overview
Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens.
Toxoplasma
counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poorly characterized. We identified ROP55, a rhoptry protein that promotes parasite survival by preventing lytic cell death in absence of IFN-γ stimulation. RNA-Seq analysis revealed that ROP55 acts as a repressor of host pro-inflammatory responses. In THP-1 monocytes ΔROP55 infection increased NF-κB p65 nuclear translocation, IL-1β production, and GSDMD cleavage compared to wild type or complemented parasites. ΔROP55 infection also induced RIPK3-dependent necroptosis in human and mouse primary macrophages. Moreover, ΔROP55 parasites were significantly impaired in virulence in female mice and prevented NF-κB activation and parasite clearance in mBMDM. These findings place ROP55 as a major virulence factor, dampening lytic cell death and enabling
Toxoplasma
to evade clearance from infected cells.
Ruivo et al uncover a
Toxoplasma
survival mechanism conserved across different cell types and species. By repressing NF-kB activation and lytic host cell death pathways, the rhoptry protein ROP55, promotes parasite survival and host immune evasion.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/109
/ 38/77
/ 38/88
/ 45/29
/ 45/41
/ 45/77
/ 45/91
/ 96/106
/ 96/21
/ Animals
/ Female
/ Humanities and Social Sciences
/ Humans
/ Interleukin-1beta - metabolism
/ Mice
/ Microbiology and Parasitology
/ Proteins
/ Protozoan Proteins - genetics
/ Protozoan Proteins - metabolism
/ Receptor-Interacting Protein Serine-Threonine Kinases - metabolism
/ Science
/ Survival
/ Toxoplasmosis - parasitology
/ Transcription Factor RelA - metabolism
/ Virulence Factors - genetics
